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A comprehensive non-redundant gene catalog reveals extensive within-community intraspecies diversity in the human vagina.

Bing Ma | Michael T France | Jonathan Crabtree | Johanna B Holm | Michael S Humphrys | Rebecca M Brotman | Jacques Ravel
Nature communications | 2020

Analysis of metagenomic and metatranscriptomic data is complicated and typically requires extensive computational resources. Leveraging a curated reference database of genes encoded by members of the target microbiome can make these analyses more tractable. In this study, we assemble a comprehensive human vaginal non-redundant gene catalog (VIRGO) that includes 0.95 million non-redundant genes. The gene catalog is functionally and taxonomically annotated. We also construct a vaginal orthologous groups (VOG) from VIRGO. The gene-centric design of VIRGO and VOG provides an easily accessible tool to comprehensively characterize the structure and function of vaginal metagenome and metatranscriptome datasets. To highlight the utility of VIRGO, we analyze 1,507 additional vaginal metagenomes, and identify a high degree of intraspecies diversity within and across vaginal microbiota. VIRGO offers a convenient reference database and toolkit that will facilitate a more in-depth understanding of the role of vaginal microorganisms in women's health and reproductive outcomes.

Pubmed ID: 32103005

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This is a list of tools and resources that we have found mentioned in this publication.


BLASTN (tool)

RRID:SCR_001598

Web application to search nucleotide databases using a nucleotide query. Algorithms: blastn, megablast, discontiguous megablast.

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eggNOG (tool)

RRID:SCR_002456

A database of orthologous groups of genes. The orthologous groups are annotated with functional description lines (derived by identifying a common denominator for the genes based on their various annotations), with functional categories (i.e derived from the original COG/KOG categories). eggNOG's database currently counts 1.7 million orthologous groups in 3686 species, covering over 7.7 million proteins (built from 9.6 million proteins). (Jan 30, 2014)

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GenBank (tool)

RRID:SCR_002760

NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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SMART Video-tracking (tool)

RRID:SCR_002852

Software for the automated evaluation of behavior in a range of pre-clinical and neuroscience applications in basic and clinical psychopharmacology. Applications include phenotype characterization and studying the behavioral effects of pharmacologic substances.

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IMG System (tool)

RRID:SCR_002965

Resource for analysis and annotation of genome and metagenome datasets in comprehensive comparative context. IMG provides users with tools for analyzing publicly available genome datasets and metagenome datasets.

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PROSITE (tool)

RRID:SCR_003457

Database of protein families and domains that is based on the observation that, while there is a huge number of different proteins, most of them can be grouped, on the basis of similarities in their sequences, into a limited number of families. Proteins or protein domains belonging to a particular family generally share functional attributes and are derived from a common ancestor. It is complemented by ProRule, a collection of rules based on profiles and patterns, which increases the discriminatory power of profiles and patterns by providing additional information about functionally and/or structurally critical amino acids. ScanProsite finds matches of your protein sequences to PROSITE signatures. PROSITE currently contains patterns and profiles specific for more than a thousand protein families or domains. Each of these signatures comes with documentation providing background information on the structure and function of these proteins. The database is available via FTP.

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Pfam (tool)

RRID:SCR_004726

A database of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). Users can analyze protein sequences for Pfam matches, view Pfam family annotation and alignments, see groups of related families, look at the domain organization of a protein sequence, find the domains on a PDB structure, and query Pfam by keywords. There are two components to Pfam: Pfam-A and Pfam-B. Pfam-A entries are high quality, manually curated families that may automatically generate a supplement using the ADDA database. These automatically generated entries are called Pfam-B. Although of lower quality, Pfam-B families can be useful for identifying functionally conserved regions when no Pfam-A entries are found. Pfam also generates higher-level groupings of related families, known as clans (collections of Pfam-A entries which are related by similarity of sequence, structure or profile-HMM).

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MetaPhlAn (tool)

RRID:SCR_004915

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Computational tool for profiling the composition of microbial communities from metagenomic shotgun sequencing data. It relies on unique clade-specific marker genes identified from reference genomes.

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Bowtie (tool)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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SILVA (tool)

RRID:SCR_006423

High quality ribosomal RNA databases providing comprehensive, quality checked and regularly updated datasets of aligned small (16S/18S, SSU) and large subunit (23S/28S, LSU) ribosomal RNA (rRNA) sequences for all three domains of life (Bacteria, Archaea and Eukarya). Supplementary services include a rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. The extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches. Alignment tool, SINA, is available for download as well as available for use online.

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NCBI (tool)

RRID:SCR_006472

A portal to biomedical and genomic information. NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease.

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InterPro (tool)

RRID:SCR_006695

Service providing functional analysis of proteins by classifying them into families and predicting domains and important sites. They combine protein signatures from a number of member databases into a single searchable resource, capitalizing on their individual strengths to produce a powerful integrated database and diagnostic tool. This integrated database of predictive protein signatures is used for the classification and automatic annotation of proteins and genomes. InterPro classifies sequences at superfamily, family and subfamily levels, predicting the occurrence of functional domains, repeats and important sites. InterPro adds in-depth annotation, including GO terms, to the protein signatures. You can access the data programmatically, via Web Services. The member databases use a number of approaches: # ProDom: provider of sequence-clusters built from UniProtKB using PSI-BLAST. # PROSITE patterns: provider of simple regular expressions. # PROSITE and HAMAP profiles: provide sequence matrices. # PRINTS provider of fingerprints, which are groups of aligned, un-weighted Position Specific Sequence Matrices (PSSMs). # PANTHER, PIRSF, Pfam, SMART, TIGRFAMs, Gene3D and SUPERFAMILY: are providers of hidden Markov models (HMMs). Your contributions are welcome. You are encouraged to use the ''''Add your annotation'''' button on InterPro entry pages to suggest updated or improved annotation for individual InterPro entries.

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ProDom (tool)

RRID:SCR_006969

Comprehensive set of protein domain families automatically generated from UniProt Knowledge Database. Automated clustering of homologous domains generated from global comparison of all available protein sequences.

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IMG (tool)

RRID:SCR_007733

Datasets and tools for comparative analysis and annotation of all publicly available genomes from three domains of life in a uniquely integrated context. Plasmids that are not part of a specific microbial genome sequencing project and phage genomes are also included in order to increase its genomic context for comparative analysis. The user interface (see User Interface Map) allows navigating the microbial genome data space along its three key dimensions (genes, genomes, and functions), and groups together the main comparative analysis tools. Microbial genome data analysis in IMG usually starts with the definition of an analysis context in terms of selected genomes, functional annotations, and/or genes, followed by the individual or comparative analysis of genomes, functional annotations, or genes.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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Trimmomatic (tool)

RRID:SCR_011848

Software Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.

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IDBA-UD (tool)

RRID:SCR_011912

Software for an iterative De Bruijn Graph De Novo Assembler for Short Reads Sequencing data with Highly Uneven Sequencing Depth.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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MP Biomedicals (tool)

RRID:SCR_013308

An Antibody supplier

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MobiDB (tool)

RRID:SCR_014542

A database of protein disorder and mobility annotations. The database features three levels of annotation: manually curated data (which are extracted from the DisProt database), indirect data, and predicted data. Additional annotations are included from external sources, including UniProt, Pfam, PDB, and STRING.

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BMTagger (tool)

RRID:SCR_014619

A tool that discriminates between human reads and microbial reads without performing an alignment of all reads to the human genome.

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